1. Field of the Invention
The present invention relates to a dipeptide derivative and a prophylactic or therapeutic agent for bone diseases containing the same as an active ingredient.
2. Description of the Related Art
In recent years, the rapid increase in the number of aged people in the population has caused an increase in so-called geriatric diseases. Among these diseases, bone diseases including osteoporosis are accompanied by a higher incidence of bone fracture, and this has been the major cause of the increase of aged patients who are bed-ridden. Therefore, there is an urgent need for a pharmaceutical composition for preventing and treating the above-mentioned bone diseases.
Bone is not a tissue which does not undergo any change once formed. The structure and the amount of bone is maintained due to the balance between osteogenesis and bone resorption. When this balance is lost due to aging or some other factors, various bone diseases are induced. Examples of diseases due to abnormal sthenia of bone resorption include malignant hypercalcemia caused by myeloma or lymphoma, bone Paget's disease caused by local bone resorption, and osteoporosis in aged people accompanied by a decrease in bone weight, though the causes of this disease are as yet unknown.
Bones mainly comprise organic matter of collagen fibers and the inorganic matter of calcium salts. The two are combined and form bones, constructions which are highly resistant against tension and pressure. In particular, calcium salts amount to 70% of the total bone weight. In bone diseases, calcium salts tend to dissolve into the blood and thus are slowly lost as the diseases proceed. Known methods for preventing or treating these diseases comprise supplying calcium or maintaining the normal calcium level.
For the prevention or treatment of such diseases, up to now use has been made of the method of treatment of supplementing or maintaining the calcium. Use has been made of active vitamin D.sub.3 preparations and calcium preparations for this. Further, hormone preparations such as estrogen and calcitonin preparations have been used in order to suppress decalcification of bones.
In addition to the above-mentioned therapeutic methods, the importance of prevention of the decrease in collagen fibers in bone diseases has been recently noted. Namely, recent studies have revealed the decomposition enzyme for collagen fiber which is contained in bones as the matrix, and attempts have been made to use an inhibitor of that decomposition enzyme for the treatment of resorption type bone diseases (see Japanese Unexamined Patent Publication (Kokai) No. 63-284127 and Japanese Unexamined Patent Publication (Kokai) No. 2-218619). It was only recently, however, that it became clear that collagen type I, which is contained in bones as the matrix, is decomposed by cathepsin L, which is a thiol protease found among lysosomal enzymes (see Nobuhiko Katsunuma, Gakushikai Kaiho, no. 792, pp. 48 to 52, 1991). These studies have just recently been concluded and no report has been made of examples of actual treatment of patients. No practical therapeutic agent has yet been provided.